Germline DNA copy number variation in familial and early-onset breast cancer

Introduction

Genetic factors predisposing individuals to cancer remain elusive in the majority of patients with a familial or clinical history suggestive of hereditary breast cancer. Germline DNA copy number variation (CNV) has recently been implicated in predisposition to cancers such as neuroblastomas as well as prostate and colorectal cancer. We evaluated the role of germline CNVs in breast cancer susceptibility, in particular those with low population frequencies (rare CNVs), which are more likely to cause disease."

Methods

Using whole-genome comparative genomic hybridization on microarrays, we screened a cohort of women fulfilling criteria for hereditary breast cancer who did not carry BRCA1/BRCA2 mutations.

Results

The median numbers of total and rare CNVs per genome were not different between controls and patients. A total of 26 rare germline CNVs were identified in 68 cancer patients, however, a proportion that was significantly different (P = 0.0311) from the control group (23 rare CNVs in 100 individuals). Several of the genes affected by CNV in patients and controls had already been implicated in cancer.

Conclusions

This study is the first to explore the contribution of germline CNVs to BRCA1/2-negative familial and early-onset breast cancer. The data suggest that rare CNVs may contribute to cancer predisposition in this small cohort of patients, and this trend needs to be confirmed in larger population samples.     

Prognosis of T3N0M0 small-cell non-anaplastic bronchogenic carcinoma

We analyzed the survival after surgery for non-small cell lung cancer (NSCLC) classified as T3N0. Between January 1969 and 1995, 151 patients underwent surgery for NSCLC in our hospital. Survival analysis was performed using the Kaplan-Meier statistical method and the curves were compared using Mantel-Cox, Breslow and Tarone-Ware tests. The estimated five-year survival in the studied population was 44.46 +/- 4.30%. Four groups were defined based on degree of tumoral invasion of mediastinal structures, parietal pleura, chest wall or superior sulcus. Significant differences in five-year survival were observed between groups. Patients in the mediastinal group (59.98 +/- 8.71%) had the best prognosis, followed by patients with parietal pleura involvement (52.79 +/- 6.69%). Survival in the chest wall group was 27.53 +/- 7.22%. No patients with superior sulcus tumors survived over five years (median survival 1.50 +/- 1.16 years; 95% confidence interval 0.00 to 3.77 years). Prognosis is clearly determined by degree of tumoral invasion in T3N0 patients. In spite of the evident conceptual improvements achieved with the revised International Staging System, the system still fails to fully define prognosis in such cases.     

Routine isotropic computed tomography scanning of the abdomen and pelvis

For 30 years, abdominal CT has been imaged and reviewed in the axial plane. It is now possible to carry out isotropic imaging of the whole abdomen and pelvis using a 40‐channel scanner. This allows creation of coronal and sagittal reformats with the same image quality as the axial images. In this study, we present our experience of reviewing routinely coronal and, occasionally, sagittal reformats. We discuss situations where these nonaxial reformats are most beneficial.     

Thoracic venous aneurysms. Clinical observation

Venous aneurysms are infrequent vascular alterations. Their origin is not well known, but pathologic study reveals probably a similar natural history than the arterial aneurysms. Their clinical significance arises from the complications they can originate, specially in certain locations, which include pulmonary embolism, and, on the other hand, differential diagnosis with certain malignant pathologies may be necessary, depending upon the clinical context. A patient is presented whose radiographic findings, in association with clinical factors, led to surgical exploration to rule out malignant lung tumor. A left subclavian vein aneurysm was finally diagnosed using magnetic resonance imaging.     

Contrast venography: reassessment of its role

To compare contrast venography with noninvasive methods, 353 patients clinically suspected of having deep venous thrombosis were examined with venography and independently with combined Doppler flow sounds and plethysmography. Noninvasive examinations had a sensitivity of 96% and a specificity of 90%. Positive noninvasive tests had a 94% predictive value, and negative noninvasive tests had a 93% predictive value. The overall accuracy of the noninvasive tests was 94% (331 of 353) compared with venography. Since venography itself may be subject to misinterpretation, noninvasive examinations should be the preferred initial method for diagnosing deep venous thrombosis. Venography should be reserved for situations that require additional diagnostic confirmation.